Hepatitis C virus (HCV) infections pose a growing challenge to health care systems. Although chronic HCV infection begins as an asymptomatic condition with few short-term effects, it can progress to cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC), and death. The rate of new HCV infections is decreasing, yet the number of infected people with complications of the disease is increasing. In the United States, people born between 1945 and 1964 (baby boomers) are developing more complications of infection. Men and African Americans have a higher prevalence of HCV infection. Progression of fibrosis can be accelerated by factors such as older age, duration of HCV infection, sex, and alcohol intake. Furthermore, insulin resistance can cause hepatic steatosis and is associated with fibrosis progression and inflammation. If more effective therapies are not adopted for HCV, more than 1 million patients could develop HCV-related cirrhosis, hepatic decompensation, or HCC by 2020, which will impact the US health care system. It is important to recognize the impact of HCV on liver disease progression and apply new therapeutic strategies.

Introduction

Approximately 180 million people worldwide are infected with hepatitis C virus (HCV) and are at risk of developing serious hepatic complications such as cirrhosis, hepatocellular carcinoma (HCC), or decompensation. In the United States, HCV-related end-stage liver disease is the most common indication for transplantation, and HCV markers are frequently found in cases of HCC. Although some data suggest that hepatitis C does not increase overall mortality, it has been postulated that HCV infection could result in an 8- to 12-year reduction in life expectancy. It is estimated that HCV caused more than 86,000 deaths in the European region in 2002. The prevalence of hepatitis C–related cirrhosis and its complications is expected to continue to increase through the next decade. In addition, demographic changes are expected to result in an increasing incidence of severe HCV-related liver disease as the population ages.

Various estimates of HCV prevalence in the US population place the number of infected individuals (as defined by anti-HCV antibody positivity) at between 4.1 and 5 million. Of these, 3.2–3.4 million are chronically infected. During the first 10–20 years of infection HCV-infected individuals generally experience asymptomatic or mild illness, which explains why an estimated 75% of infections remain undiagnosed in the United States. Despite a decline in the number of new US cases of HCV infection from a peak of an estimated 262,000/year in 1986 to 17,000/year in 2007, the prevalence of individuals infected with HCV for more than 20 years is expected to continue to increase until 2015. In the National Health and Nutrition Examination Survey (NHANES; 1999–2002), patients aged 40–49 years accounted for 66% of American HCVinfected patients, and the prevalence of HCV infection in the United States was 2.7 times higher among 40- to 49-year-olds than the general population. This "baby boomer" generation is particularly susceptible to blood-borne HCV transmission as a result of an increased lifetime risk of injection drug use (IDU), blood transfusion before 1992, or sexual activity with =20 partners, compared with older or younger patients. The prevalence of HCV infection varies by age, sex, and race/ethnicity, and early identification of at-risk individuals through routine questioning by clinicians is critical, because management options are limited in late-stage disease.

After 30 years of infection, an estimated 15%–35% of patients will develop cirrhosis (5-year survival, 75%–80%); after 40 years, up to 60% could have cirrhosis. Given the high prevalence of HCV infection among 40- to 49-year-olds and that Americans are now expected to live into their mid-70s or beyond, the incidence of complications of HCV infections can be expected to further increase in coming years. In fact, from 1995–2004, US HCV-related mortality already increased 123% from 1.09/100,000 to 2.44/100,000 persons, although this study has some limitations. Furthermore, the proportion of CHC patients in the United States with cirrhosis is projected to rise from 25% in 2010 to 45% in 2030. Projections also estimate that without effective treatment, the annual number of US patients with cirrhosis, hepatic decompensation, or HCC will roughly double by 2020, and liver-related deaths will almost triple. Although not all data agree with these estimates, several studies have suggested that HCV infection could have a deleterious effect on population mortality rates and life expectancy. HCV increased the risk of death in several analyses, irrespective of comorbidities such as coinfection with human immunodeficiency virus (HIV) or hepatitis B virus (HBV) and even after adjustment for alcohol consumption. Furthermore, numerous studies and a Cochrane review indicated that achievement of an SVR through effective antiviral therapy can significantly reduce mortality in patients with chronic HCV. If all HCV-infected patients were treated with currently available treatment in 2010, liver-related HCV-associated deaths could be reduced by 36% by 2020, whereas antiviral treatment rates are currently declining. Improvements in diagnosis and treatment are therefore necessary to reduce the associated public health burden.

Individuals with CHC are at increased risk of liverrelated morbidity and mortality. HCV infection was associated with 27% of all US liver transplants performed in 2007, and US-based studies demonstrated that up to 51%–55% of HCC patients have anti-HCV antibodies. There is also a link between steatosis and liver fibrosis in HCV-infected patients, as well as a potential association between HCV infection and HCC or, as described more recently, of intrahepatic cholangiocarcinoma (ICC). In some ethnic groups such as Latinos the course of HCV infection is more aggressive, with a higher risk of cirrhosis than other ethnic groups. Furthermore, disease progression is more rapid in patients who are coinfected with HCV and HIV. Coinfected patients have approximately double the risk of cirrhosis or decompensation than those infected with HCV alone.